Probing regio- and enantioselectivity in the formal [2+2] cycloaddition of C(1)-alkyl ammonium enolates with - and ,-substituted tri-fluoromethylenones
Abstract
The isothiourea-catalyzed regio- and enantioselective formal [2 + 2] cycloaddition of C(1)-alkyl and C(1)-unsubstituted ammonium enolates with β- and α,β-substituted trifluoromethylenones has been developed. In all cases, preferential [2 + 2]-cycloaddition over the alternative [4 + 2]-cycloaddition is observed, giving β-lactones with excellent diastereo- and enantioselectivity (34 examples, up to >95:5 dr, >99:1 er). The regioselectivity of the process was dictated by the nature of the substituents on both reaction components. Solely [2 + 2] cycloaddition products are observed when using α,β-substituted trifluoromethylenones or α-trialkylsilyl acetic acid derivatives; both [2 + 2] and [4 + 2] cycloaddition products are observed when using β-substituted trifluoromethylenones and α-alkyl-α-trialkylsilyl acetic acids as reactants, with the [2 + 2] cycloaddition as the major reaction product. The beneficial role of the α-silyl substituent within the acid component in this protocol has been demonstrated by control experiments.
Citation
Wang , Y , Young , C M , Cordes , D B , Slawin , A M Z & Smith , A D 2023 , ' Probing regio- and enantioselectivity in the formal [2+2] cycloaddition of C(1)-alkyl ammonium enolates with - and ,-substituted tri-fluoromethylenones ' , The Journal of Organic Chemistry , vol. 88 , no. 12 , pp. 7784-7799 . https://doi.org/10.1021/acs.joc.2c02688
Publication
The Journal of Organic Chemistry
Status
Peer reviewed
ISSN
0022-3263Type
Journal article
Rights
Copyright © 2023 The Authors. Published by American Chemical Society under CC BY.
Description
Funding: UK Engineering and Physical Sciences Research Council - EP/S019359/1; China Scholarship Council.Collections
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